Tuberous sclerosis complex and Wolff-Parkinson-White syndrome

This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways.     

Double Outlet Right Ventricle with Intact Atrial Septum and Restrictive Ventricular Septal Defect: An Analysis of Two Cases

Two cases of double outlet right ventricle with restrictive ventricular septal defect are described. This is an uncommon presentation that causes left ventricular dysfunction because of left ventricular outflow tract obstruction. The presence of an intact atrial septum leads to severe pulmonary hypertension, which tends to aggravate the right ventricular output. In the presence of a normal left ventricle, the authors suggest the possibility of enlargement of the ventricular septal defect in order to perform a biventricular repair. The association of a supramitral valve ring in both cases, and the isolation of the left subclavian artery and an aortopulmonary fenestration in one of these cases, are also discussed. In addition we explore factors that cause restrictive ventricular septal defects as well as the mechanisms that may lead to spontaneous closure of ventricular septal defect in a double outlet right ventricle.     

Iron-induced oxidative DNA damage and its repair in primary rat hepatocyte culture

Iron-overload diseases frequently develop hepatocellular carcinoma. The genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might involve an oxidative process via the intermediate production of reactive oxygen species. This was presently investigated by examining kinetics of formation and repair of DNA base lesions in primary rat hepatocyte cultures supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and 100 microM). Seven DNA base oxidation products have been identified in DNA extracts by gas chromatography- mass spectrometry, which showed a predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine, 2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil, 5-OH-cytosine) in control cultures. All these DNA oxidation products revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA supplementation, among which fapy-adenine showed the highest increase and 5-OH-cytosine was the least prominent. Involvement of iron in this oxidative process was established by a correlation between extent in DNA oxidation and intracellular level of toxic low molecular weight iron. DNA excision- repair activity was estimated by release of DNA oxidation products in culture medium. All the seven DNA oxidation products were detected in the medium of control cultures and showed basal repair activity. This DNA repair activity was increased in a time- and dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was 5-OHMe-Uracil, were preferentially repaired, which explains the low levels detected in oxidized DNA. Since oxidized bases substantially differed from one another in terms of excision rates from cellular DNA, specific excision- repair enzymes might be involved. Our findings, however, demonstrate that even though DNA repair pathways were activated in iron-loaded hepatocyte cultures, these processes were not stimulated enough to prevent an accumulation of highly mutagenic DNA oxidative products in genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in understanding the hepatocarcinogenic evolution of iron-overload diseases.      

Intravenous Leiomyomatosis of the Uterus

Three cases of intravenous leiomyomatosis (IVL) of the uterus, a rare benign smooth-muscle tumor, are described. A preoperative diagnosis of IVL was not made in any of the patients, all of which presented with a pelvic mass with the presumptive diagnosis of leiomyoma. Surgical exploration confirmed the presence of uterine mass and two of the three cases showed extra-uterine extension into the ovarian or uterine veins. Histological examination demonstrated a fascicular pattern of bland spindle-shaped smooth-muscle cells, which extended to veins inside the myometrium or to extrauterine veins. This was confirmed by immunohistochemical stain for desmin and factor VIII. Despite their histological benignity, these lesions have a tendency to metastasize and are closely related to the conditions called “benign metastasizing leiomyoma” and “intracaval mass and cardiac extension”. The primary treatment of IVL is hysterectomy and excision of any extrauterine tumor, when technically feasible. Anti-estrogenic therapy has been suggested as potentially useful in controlling of unresectable tumor. According to the literature, the follow-up must be long and periodic postoperative ultrasonic or magnetic nuclear resonance imaging studies may be useful in detecting growth of residual intravascular tumor.     

Guanosine and GMP prevent seizures induced by quinolinic acid in mice

In the mammalian CNS, glutamate and GABA are the principal neurotransmitters mediating excitatory and inhibitory synaptic events, respectively, and have been implicated in the neurobiology of seizures. Guanine-based purines, including the nucleoside guanosine and the nucleotide GMP, have been shown to antagonize glutamatergic activity at the receptor level and the other purine nucleoside adenosine is a well-known modulator of seizure threshold. In the present study we investigated the anticonvulsant effect of i. p. guanosine and GMP against seizures induced by the glutamate agonist quinolinic acid (QA) or the GABA(A) antagonist picrotoxin in mice. Animals were pretreated with an i.p. injection of saline, guanosine or GMP 30 min before either an i.c.v. injection of 4 microliter QA (36.8 nmol) or a subcutaneous injection of picrotoxin (3.2 mg/kg). All animals pretreated with vehicle followed by QA or picrotoxin presented seizures, which were completely prevented by the NMDA antagonist MK-801 and the GABA agonist phenobarbital, respectively. Guanosine and GMP dose-dependently protected against QA-induced seizures, up to 70 and 80% at 7.5 mg/kg, with ED(50)=2. 6+/-0.4 and 1.7+/-0.6 mg/kg, respectively. Conversely, neither guanosine, GMP nor MK-801 affected picrotoxin-induced seizures, indicating some degree of specificity towards the glutamatergic system. This study suggests anticonvulsant properties of i.p. guanosine and GMP, which may be related with antagonism of glutamate receptors.     

Optimal management of complicated empyema

BACKGROUND: Despite continued improvement in medical therapy, empyema remains a challenging problem for the surgeon. Multiple treatment options are available; however, the optimal therapeutic management has not been elucidated. METHODS: A retrospective review was performed of all adult patients admitted to Denver Health Medical Center between January 1, 1993, and December 31, 1998, with the diagnosis of empyema. Data tabulated included patient demographics, presentation, chest computed tomography (CT) findings, treatment, and outcome. RESULTS: Empyema was diagnosed in 58 patients, 45 cases of which were multiloculated at the time of presentation. Empyema was secondary to pneumonia is 41 patients and posttraumatic in 15. In addition to antibiotic therapy, initial treatment included chest tube drainage alone (n = 6), chest tube drainage with primary operation (n = 19), and chest tube drainage with intrapleural fibrinolytic therapy (n = 33). In 15 patients (45%), fibrinolytic therapy failed. Initial chest CT revealed a pleural peel in 5 patients treated with fibrinolytics and all failed. Multiloculation, however, was not a factor in failure of fibrinolysis. Moreover, chest CT missed the presence of a pleural peel in 17 of 31 patients documented to have a significant peel at the time of thoracotomy. CONCLUSION: Multiple therapeutic options are available for the management of empyema. Multiloculation is not a contraindication to an initial trial of chest tube drainage or fibrinolytic therapy. In contrast, CT evidence of a pleural peel uniformly predicted failure of nonoperative treatment.     

The use of the female condom by women in Brazil participating in HIV prevention education sessions.

OBJECTIVES: To study HIV-positive women and women at risk of becoming infected with HIV who attended HIV prevention education group sessions at a university hospital in Brazil and to compare the use of the female condom and the male condom by these two groups of women. METHODS: The study subjects were 165 women participating in HIV prevention education group sessions at the Medical School Hospital of Ribeir?o Preto of the University of S?o Paulo, in the city of Ribeir?o Preto, S?o Paulo, Brazil. Women could be enrolled in the study from August 2000 to June 2001, and the follow-up observation time period was from August 2000 to July 2001. Male condoms and female condoms were freely distributed to all the participants at the end of each educational session and also at the end of each follow-up visit that the participants made. Each woman took part in an initial interview and was asked to return monthly. At each follow-up visit an additional short interview was carried out in order to investigate use of the male condom and of the female condom. Variables that were examined for the study included age, education, ethnic group, marital or relationship status, number of children, the women's use of male condoms and female condoms, commercial sex (whether the women had ever had sex in exchange for money, gifts, or favors), and previous knowledge of the female condom. RESULTS: The 165 women studied fell into the following three categories: 132 of them (80.0%) were HIV-positive, 26 of them (15.8%) had a sexually transmitted disease (STD) other than HIV and did not have an HIV-positive partner, and 7 of them (4.2%) had an HIV-positive partner but did not have HIV or any other STD. The women ranged in age from 15 to 64 years, with a mean of 30.3 years. Of the women in the study, 69.7% of them were married or were cohabitating, and 90.9% of them had a sexual partner. Just over two-thirds of the women had seven years of formal schooling or less. Out of 163 women, a total of 31 of them (19.0%) had never used the male condom with a partner, and 49 of the 163 (30.1%) had not used a male condom at the time of the last sexual intercourse. Out of the 165 women, 74 of them (44.8%) returned for at least one follow-up visit. Of these 74 women, 58 of them (78.3%) reported using the female condom between the initial interview and the first follow-up visit. The majority of the 74 women who returned for a visit liked using the female condom, and the women reported that their partners also generally accepted the female condom. In comparison to women at risk of HIV, HIV-positive women were more likely to have used the male condom with a partner before the initial interview. Women who continued returning over a longer follow-up period were more likely to have used the female condom at the time of the last sexual intercourse. No association was found between female condom use at the time of last sexual intercourse and the woman's HIV infection status. CONCLUSIONS: In comparison to the women at risk of HIV, the HIV-positive women in our study were more likely to use male condoms with their partners, to return for follow-up visits, and to have a longer follow-up period. The acceptance of the female condom among the HIV-positive women in this study, as reported at their first follow-up visit, appears to be similar to the acceptance of the female condom among women in general in Brazil.     

Gut ischemia/reperfusion activates lung macrophages for tumor necrosis factor and hydrogen peroxide production

BACKGROUND: Gut ischemia followed by reperfusion (I/R) is implicated as a prime initiating event in the mechanism of multiple organ failure after trauma and hemorrhagic shock. Several lines of evidence indicate that macrophages are involved in this prime event. Our purpose was to evaluate hydrogen peroxide (H2O2) and tumor necrosis factor (TNF) production and phagocytosis by lung macrophages in a gut I/R model of multiple organ failure in rats. METHODS: In the experimental group (I/R), Wistar rats (n = 35) were anesthetized and subjected to a median laparotomy, and the superior mesenteric artery was clamped for 45 minutes followed by 60 minutes of reperfusion. In the control group (LAP) (n = 37), animals underwent sham laparotomy. After the period of reperfusion, bronchoalveolar lavage (BAL) was performed and the resulting BAL cells were assayed for H2O2 production using the horseradish peroxidase-mediated red phenol oxidation method. TNF release was determined using the L929 cells bioassay. Zymosan phagocytosis by BAL macrophages was quantitated using phase microscopy. RESULTS: H2O2 release in BAL cells of I/R rats (19.90 +/- 7.98 nmol/L/2 x 10(5) cells) is statistically higher than in the LAP group (10.92 +/- 5.01 nmol/L per 2 x 10(5) cells) (p = 0.0155), and the TNF production by BAL cells of the I/R group (38.09 +/- 20.79 units per 10(6) cells) was significantly higher than that of LAP rats (17.16 +/- 13.35 units per 10(6) cells) (p = 0.0281). Phagocytic activity of BAL mac. Macrophages of I/R rats was not statistically different from LAP animals. CONCLUSION: These results suggest that BAL macrophage play a role in the mechanism of acute lung injury after trauma and hemorrhagic shock.     

Panniculitis in childhood and adolescence

Background: The purpose of the present paper was to describe the clinical manifestations and treatment of patients with panniculitis. Methods: From January 1983 to December 2002, 4294 patients were treated for pediatric rheumatological diseases at Pediatric Rheumatology Unit, University of São Paulo, Brazil. Of these, 35 children and adolescents (0.8%) presented with panniculitis: erythema nodosum (EN) or Weber–Christian disease (WCD). Clinical characteristics, laboratory exams, biopsy of the lesion, treatment and clinical course were studied. Results: Of the 35 patients, 29 presented with EN and six with WCD, one of these with cytophagic histiocytic panniculitis. Mean age at symptom onset was 85 months (6–204 months) and the mean duration of follow up was 55 months (1–144 months). All the patients presented with inflammatory subcutaneous nodules. The patients with WCD presented with systemic manifestations and cutaneous atrophy. The principal etiologies of EN were streptococcal infection (42%), undetermined (13.5%), pulmonary tuberculosis (10%), and acute rheumatic fever (10%). Biopsy of the nodules indicated septal panniculitis in 14 patients with EN and lobular panniculitis without vasculitis in the patients with WCD, one of which had cytophagic histiocytic panniculitis. There was recurrence in 11 patients (38%) with EN and in all those with WCD. Non‐steroidal anti‐inflammatory drugs were used in 15 patients with EN and corticosteroids and/or immunosuppressive drugs in the six patients with WCD. Three patients died. Conclusions: EN is the most frequent panniculitis, with a benign course and is mainly associated with infections. WCD is a severe disease, with systemic involvement, that proceeds with cutaneous atrophy and requires the use of corticosteroids and or immunosuppressive drugs.     

Structural and biological characterization of three novel mastoparan peptides from the venom of the neotropical social wasp Protopolybia exigua (Saussure).

The venom of the Neotropical social wasp Protopolybia exigua(Saussure) was fractionated by RP-HPLC resulting in the elution of 20 fractions. The homogeneity of the preparations were checked out by using ESI-MS analysis and the fractions 15, 17 and 19 (eluted at the most hydrophobic conditions) were enough pure to be sequenced by Edman degradation chemistry, resulting in the following sequences: Protopolybia MPI I-N-W-L-K-L-G-K-K-V-S-A-I-L-NH2 Protopolybia-MP II I-N-W-K-A-I-I-E-A-A-K-Q-A-L-NH2 Protopolybia-MP III I-N-W-L-K-L-G-K-A-V-I-D-A-L-NH2 All the peptides were manually synthesized on-solid phase and functionally characterized. Protopolybia-MP I is a hemolytic mastoparan, probably acting on mast cells by assembling in plasma membrane, resulting in pore formation; meanwhile, the peptides Protopolybia-MP II and -MP III were characterized as a non-hemolytic mast cell degranulator toxins, which apparently act by virtue of their binding to G-protein receptor, activating the mast cell degranulation.